Protect APIs from degradation
The manufacturing process must be designed to protect APIs from physical degradation. Some APIs, such as retinoic acid compounds,
are sensitive to both ultraviolet (UV) light and oxygen. These APIs can be protected by using yellow or amber light that is
free from harmful, low-wavelength UV rays and by using nitrogen, argon, or another inert gas to purge the product of oxygen.
Identify equipment constraints
The manufacturer must be able to perform all processes using its current equipment capabilities. The scale-up path for a 1:10
batch size from the pilot or clinical size to commercial level must exist with similar equipment. Guidance from FDA's Scale-Up
and Postapproval Changes Semisolids (SUPAC-SS) Working Group provides the basis of comparison for the design and operating
principles of equipment (1).
Consider regulatory requirements
Satisfying regulatory requirements for the scale-up or transfer of a process can be challenging. To scale up a process used
for clinical batch manufacturing or transfer a commercial process to a new manufacturing site, the equipment must at least
be of the same materials of construction and employ the same type of mixing, as defined in the SUPAC-SS guidance (1).
Using an outsourcing partner
The manufacturing process can influence a topical product's stability and performance. If a formulation is transferred to
a contract manufacturer, changes in mixing speeds, temperature controls, and order of ingredient addition may be needed. Outsourcing
formulation development and manufacturing to a contract development and manufacturing organization allows technology transfer,
scale-up, and manufacturing to take place at one location, which ensures project continuity.
Michael Lowenborg is research and development manager at DPT Laboratories, 3300 Research Plaza, San Antonio, TX 78235, tel. 210.531.7125, Michael.email@example.com
1. FDA, Nonsterile Semisolid Dosage Forms, Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Release
Testing and In Vivo Bioequivalence Documentation (Rockville, MD, May 1997).